NCCN VERSION 2 2015

The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

MS-25

NCCN Guidelines Index

Breast Cancer Table of Contents

Discussion

NCCN Guidelines Version 2.2015

Breast Cancer

of the panel is that there are insufficient data to make definitive

chemotherapy recommendations for those >70 years of age. Although

AC or CMF (cyclophosphamide/methotrexate/fluorouracil) was superior

to capecitabine in a randomized trial of women aged ≥65 years with

early-stage breast cancer, enrollment in that study was discontinued

early.

211

There is also a possibility that AC/CMF is not superior to any

chemotherapy in this cohort. Therefore, treatment should be

individualized for women in this age group, with consideration given to

comorbid conditions.

Estimating Risk of Relapse or Death and Benefits of Systemic

Treatment

Several prognostic factors predict for future recurrence or death from

breast cancer. The strongest prognostic factors are patient age,

comorbidity, tumor size, tumor grade, number of involved ALNs, and

possibly HER2 tumor status. Algorithms have been published

estimating rates of recurrence,

209

and a validated, computer-based

model (Adjuvant! Online;

www.adjuvantonline.com )

is available to

estimate 10-year DFS and OS that incorporates all of the above

prognostic factors except for HER2 tumor status.

210,212

These tools aid

the clinician in objectively estimating outcome with local treatment only,

and also assist in estimating the absolute benefits expected from

systemic adjuvant endocrine therapy and chemotherapy. These

estimates may be utilized by the clinician and patient in their shared

decision-making regarding the toxicities, costs, and benefits of systemic

adjuvant therapy.

213

A determination of the HER2 status of the tumor is recommended for

prognostic purposes for patients with node-negative breast cancer.

214

More importantly, HER2 tumor status also provides predictive

information used in selecting optimal adjuvant/neoadjuvant therapy and

in the selection of therapy for recurrent or metastatic disease (category

1). For example, retrospective analyses have demonstrated that

anthracycline-based adjuvant therapy is superior to

non-anthracycline-based adjuvant chemotherapy in patients with

HER2-positive tumors,

215-219

and that the dose of doxorubicin may be

important in the treatment of tumors that are HER2

positive.

220

Prospective evidence of the predictive utility of HER2 status in

early-stage

221-226

and metastatic breast cancer

227-229

is available for

trastuzumab-containing therapies.

Use of DNA microarray technologies to characterize breast cancer has

allowed for development of classification systems of breast cancer by

gene expression profile.

230

Five major subtypes of breast cancer have

been identified by DNA microarray gene expression profiling:

ER-positive/HER2-negative (luminal A and luminal B subtypes);

ER-negative/HER2-negative (basal subtype); HER2-positive; and

tumors that have characteristics similar to normal breast tissue.

231-233

retrospective analyses, these gene expression subtypes are associated

with differing relapse-free survival and OS.

Another gene-based approach is the 21-gene assay using reverse

transcription polymerase chain reaction (RT-PCR) on RNA isolated from

paraffin-embedded breast cancer tissue (Oncotype DX). On

retrospective analysis of two trials (NSABP B-14 and B-20) performed in

women with hormone receptor-positive, ALN-negative invasive breast

cancer, this assay system was able to quantify risk of recurrence as a

continuous variable (eg, Oncotype DX recurrence score) and to predict

responsiveness to both tamoxifen and CMF or

methotrexate/5-fluorouracil/leucovorin chemotherapy.

234,235

comparison of simultaneous analyses of breast cancer tumors using

five different gene-expression models indicated that four of these